Effects of 4-methylbenzylidene camphor (4-MBC) on neuronal and muscular development in zebrafish (Danio rerio) embryos
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The negative effects of overexposure to ultraviolet (UV) radiation in humans, including sunburn and light-induced cellular injury, are of increasing public concern. 4-Methylbenzylidene camphor (4-MBC), an organic chemical UV filter, is an active ingredient in sunscreen products. To date, little information is available about its neurotoxicity during early vertebrate development. Zebrafish embryos were exposed to various concentrations of 4-MBC in embryo medium for 3 days. In this study, a high concentration of 4-MBC, which is not being expected at the current environmental concentrations in the environment, was used for the purpose of phenotypic screening. Embryos exposed to 15 μM of 4-MBC displayed abnormal axial curvature and exhibited impaired motility. Exposure effects were found to be greatest during the segmentation period, when somite formation and innervation occur. Immunostaining of the muscle and axon markers F59, znp1, and zn5 revealed that 4-MBC exposure leads to a disorganized pattern of slow muscle fibers and axon pathfinding errors during the innervation of both primary and secondary motor neurons. Our results also showed reduction in AChE activity upon 4-MBC exposure both in vivo in the embryos (15 μM) and in vitro in mammalian Neuro-2A cells (0.1 μM), providing a possible mechanism for 4-MBC-induced muscular and neuronal defects. Taken together, our results have shown that 4-MBC is a teratogen and influences muscular and neuronal development, which may result in developmental defects.
Keywords4-Methylbenzylidene camphor Zebrafish embryos Somite Neuron Acetylcholinesterase Toxicity
The work described in this paper was substantially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. CityU 160110).
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Conflict of interest
The authors declare that there is no conflict of interest.
- Altringham JD, Ellerby DJ (1999) Fish swimming: patterns in muscle function. J Exp Biol 202:3397–3403Google Scholar
- Anwar K (2004) Toxic effects of cypermethrin on the development of muscle in chick embryo of Gallus domesticus. Int J Agric Biol 6:2Google Scholar
- Hanneman E, Trevarrow B, Metcalfe WK, Kimmel CB, Westerfield M (1988a) Segmental pattern of development of the hindbrain and spinal cord of the zebrafish embryo. Development 103(1):49–58Google Scholar
- Hanneman E, Trevarrow B, Metcalde WK, Kimmel CB, Westerfield M (1988b) Segmental pattern of development of the hindbrain and spinal cord of the zebrafish. Development 103(1):49–58Google Scholar
- Janjua NR, Mogensen B, Andersson AM, Petersen JH, Henriksen M, Skakkebaek NE, Wulf HC (2004) Systemic absorption of the sunscreens benzophenone-3, octylmethoxycinnamate, and 3-(4-methyl-benzylidene) camphor after whole-body topical application and reproductive hormone levels in humans. J Invest Dermatol 123(1):57–61CrossRefGoogle Scholar
- Lichtensteiger W, Ceccatelli R, Conscience M, Cotton B, Durrer S, Faass O, Fleischmann I, Ma R, Maerkel K, Schlumpf M (2002) Newly arising endocrine disruptors: UV screens and PBDE. Reprod Toxicol 16:397–398Google Scholar
- Metcalfe W, Myers P, Trevarrow B, Bass M, Kimmel C (1990) Primary neurons that express the L2/HNK-1 carbohydrate during early development in the zebrafish. Development 110:491–504Google Scholar
- Ross LS, Parrett T, Easter SS Jr (1992) Axonogenesis and morphogenesis in the embryonic zebrafish brain. J Neurosci 12:467–482Google Scholar
- Schlumpf M, Schmid P, Durrer S, Conscience M, Maerkel K, Henseler M, Gruetter M, Herzog I, Reolon S, Ceccatelli R, Faass O, Stutz E, Jarry H, Wuttke W, Lichtensteiger W (2004) Endocrine activity and developmental toxicity of cosmetic UV filters—an update. Toxicology 205:113–122CrossRefGoogle Scholar
- Sternfeld M, Ming G, Song H, Sela K, Timberg R, Poo M, Soreq H (1998) Acetylcholinesterase enhances neurite growth and synapse development through alternative contributions of its hydrolytic capacity, core protein, and variable C termini. J Neurosci 18(4):1240–1249Google Scholar
- Westerfield M (1993) A guide for the laboratory use of zebrafish Danio (Brachydanio) rerio. University of Oregon Press, Eugene, OR, USAGoogle Scholar
- Wilson SW, Ross LS, Parrett T, Easter SS Jr (1990) The development of a simple scaffold of axon tracts in the brain of the embryonic zebrafish, Brachydanio rerio. Development 108:121–145Google Scholar